10.08.2008
in Uncategorized
Protocol Numbers:
290.0504
290.0504-M
Sponsor: Lexington International, L.L.C.
Prepared by:
Eugene R. Heyman, PhD
Statistical Consultant
November 13, 2005
1. Summary
1.1 Conclusions
The results of this study showed that the HairMax LaserComb® was effective in the
promotion of hair growth and in the cessation of hair loss in males and females diagnosed
with androgenetic alopecia when treatment is applied 10-15 minutes three nonconcurring
days a week (i.e. Monday, Wednesday, Friday) for 26 weeks. The results also
demonstrated that the LaserComb is safe in these subjects.
1.2 Study Objectives
The primary aim of the study was to assess the safety and effectiveness of the HairMax
LaserComb in the promotion of hair growth and in the cessation of hair loss in males and
females diagnosed with androgenetic alopecia.
1.3 Study Design
The study was designed as a multicenter, randomized, placebo-controlled trial conducted
at four sites in the United States. Subjects who met all entry criteria were randomized in
a 2:1 fashion to receive either the HairMax LaserComb or an identical sham device that
did not emit a laser. Subjects were to use the device three times per week on
nonconcurring days for a total of 26 weeks. Hair density measurements were done at
baseline immediately prior to randomization and again at 26 weeks. Subjects who
terminated prematurely were to have had hair density measurements at their termination
visit. Additional clinic visits were scheduled at 8 and 16 weeks.
1.4 Subject Population and Demographics
The study population included males and females between the ages of 30 and 60 years
with a diagnosis of androgenetic alopecia who had been experiencing active hair loss
within the last 12 months. They were also required to have a Norwood-Hamilton
classification of IIa to V (for males) or Ebling Rook I to III (for females), and have Skin
Type I, II, III, or IV on the Fitzpatrick Skin Type Scale. A total of 123 male subjects and
16 female subjects were randomized between September 24, 2004 and February 21,
2005. Baseline demographics and clinical characteristics show that subjects randomized
to LaserComb had comparable baseline characteristics to those randomized to the
placebo.
1.5 Methods
Screened subjects who met the entry criteria returned to the study site for the baseline
visit. At this visit study personnel assessed the subject’s scalp for any signs of irritation
or dermatological conditions that would disqualify the subject from study participation.
Qualified subjects had global images taken to document hair loss since the screening
visit, had the target site area of the scalp identified and tattooed, and had a hair clipping
to determine the baseline hair density. They were then provided with their randomized
study device. Subjects returned to the clinic at 8 and 16 weeks at which adverse events
and concomitant medications were collected, vital signs were assessed, the scalp was
evaluated for local dermatitis and other scalp conditions, and subjects completed an 11question
questionnaire. At the final visit, Week 26 or the termination visit, the same
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3
procedures as weeks 8 and 16 were performed with the addition of global images with a
digital camera, hair clippings, and the investigator global assessment of new hair growth.
The protocol was originally designed for both males and females. After the study began
it was amended to only include males at the request of the FDA, and the females will be
included in a similar study with only females. The results for the 16 females treated in
this study are briefly summarized in this report. (See tables 6a, 7a, and 13 for female
results)
1.6 Results
Table 1 summarizes the principle results of effectiveness. Subjects in the LaserComb
treatment group had significantly greater increase in mean terminal hair density than
subjects in the placebo group (p<0.0001). Subjects in the LaserComb group also had
significantly better subjective assessment of overall hair regrowth than subjects in the
placebo group (p=0.010). No subject experienced a serious adverse event and the
adverse event profiles were similar between the two treatment groups.
Table 1: Principle Results of Effectiveness After 26 Weeks of Treatment
LaserComb
(N=72)
Placebo
(N=40)
P-Value
Mean Change From Baseline in
Terminal Hair Density (hairs/cm2)
in Males
18.8 -10.6 <0.0001
Subjects’ Assessment of Overall
Hair Regrowth
No Growth 36.8% 53.9% 0.010
Minimal Growth 39.5% 41.0%
Moderate Growth 22.4% 5.1%
Dense Growth 1.3% 0%
LaserComb
(N=81)
Placebo
(N=47)
P-Value
Mean Change From Baseline in
Terminal Hair Density (hairs/cm2)
in Males and Females
20.6 -8.7 <0.0001
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2. Description of Subjects
Subjects were enrolled between September 24, 2004 and February 21, 2005, according to
the following inclusion/exclusion criteria:
2.1 Inclusion Criteria
• Male with a diagnosis of androgenetic alopecia according to the Guidelines of the
American Dermatological Association; subject must have had presence of
miniaturized hair in the target area.
• Subject must have been experiencing active hair loss, within the last 12 months.
• In good general health.
• A Norwood-Hamilton classification of IIa to V.
• Skin Type I, II, III, or IV on the Fitzpatrick Skin Type Scale.
• Between 30 and 60 years of age at the time of enrollment.
• Subject must have been willing to have a dot tattoo placed on the target area of
the scalp.
• Subject must have been willing to maintain normal shampooing habits and use of
hair care products during the study.
• Subject must have been willing to maintain the same hairstyle, approximate hair
length and hair color throughout the study. If hair was colored, prospective
subject must have been willing to continue the same color and product line, not
coloring hair within 7 days prior to a visit.
• Subject was willing to continue his current regimen of vitamins and nutritional
supplements and not start any new vitamins or nutritional supplements for the
duration of the study.
• Able to read, understand, and provide written (signed) informed consent after the
nature of the study has been fully explained and before any procedures dictated by
this protocol were performed.
• Subjects must have been willing and able to comply with follow-up requirements,
including adhering to scheduled office visits in a timely manner.
• Fluent in English.
2.2 Exclusion Criteria
• An active malignancy of any type or history of any malignancy including any
malignancy in the treatment area in the past five years (subjects who had a history
of basal cell carcinoma that had been treated in areas other than the treatment area
were acceptable; subjects with a history of other malignancies that had been
surgically removed, and who had no evidence of recurrence for a least five years
before study enrollment were also acceptable).
• History of hypogonadism.
• Subject had used phytotherapy (e.g., saw palmetto) within eight weeks prior to
baseline.
• Any active skin infection in the scalp area or scarring in the target area.
• Photosensitivity to laser light.
• Subject had used Accutane® in the previous year.
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• History of poor wound healing.
• History of keloid formation.
• Known history of anticoagulant use (other than aspirin [<325 mg., QD, which is
stable for three months]).
• Subject had used or currently took any of the following medications during the six
months prior to screening: minoxidil, finasteride (or any other 5a–reductase
inhibitor medications), medications with anti-androgenic properties (e.g.,
cyproterone acetate, spironolactone, ketoconazole, flutamide, bicalutamide),
topical estrogen, progesterone, tamoxifen, anabolic steroids, medications which
can potentially cause hypertrichosis (e.g., cyclosporine, diazoxide, phenytoin,
psoralens), oral glucocorticoids (inhaled glucocorticoids are permitted), lithium,
phenothiazines, or other medications at the discretion of the Investigator.
• History of thyroid or other medical condition that might influence hair growth and
loss, at the discretion of the Investigator.
• Subject had “buzz” cut hairstyle, defined as hair cut to less than one inch in
length.
• Subject had light blonde hair, at the discretion of the investigator.
• Subject had chronic dermatological condition (eczema, psoriasis, infection, etc.)
of the scalp other than male pattern hair loss.
• Subject had a pacemaker
• Subject had hair transplants, scalp reduction, current hair weave, or tattooing in
the target area, which made it difficult to perform hair density assessments.
• Subject had ever received radiation therapy to the scalp, or had chemotherapy
within the past year.
• A known underlying medical problem that could adversely affect hair growth
such as HIV infection, connective tissue disease, and inflammatory bowel disease,
or other medical conditions, at the discretion of the investigator.
• Subject had participated in any investigational study within the 30 days prior to
randomization.
• A history or evidence of drug and/or alcohol abuse within the 12 months prior to
Visit 1.
• A history or the presence of any serious and/or chronic medical condition(s)
[including psychiatric illnesses] which, in the opinion of the investigator, may
cause harm to the individual and/or compromise/confound the study results.
3. Study Procedures
3.1 Visit 1 – Screening (Day -14)
Potential subjects read and signed informed consent and HIPAA documents. Following
the consent process, demographic and background information was collected, including
age, gender, ethnic origin and significant medical history. Additionally, all medications,
including over-the-counter drugs, taken within 6 months prior to the start of the study
were recorded. Qualified study personnel took vital signs (blood pressure and pulse).
The investigator assessed scalp condition including evaluation of Fitzpatrick Skin Type,
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and recorded hair-thinning pattern using the Norwood-Hamilton scale. Subjects
exhibiting Types IIa to V on the Norwood-Hamilton scale qualified for the study. It was
determined that subjects had some miniaturized hairs in the target area for adequate
determination of active hair loss. An evaluation was also conducted and recorded to
determine that subjects did not exhibit signs of skin/scalp conditions that would preclude
participation in the study. Global digital images were taken. The global image was used
to assist the investigator in completing the global assessment.
The subject sat in a chair (the height of the chair remained consistent throughout the
study) and was properly placed into the stereotactic apparatus. The digital images were
standardized for lighting, camera angle, and position of subject’s head in each digital
image to achieve similar camera angle and relative image size. It may have been
necessary to retake these digital images at Visit 2.
3.2 Visit 2 – Baseline (Day 0)
Subjects returned to the study site and were questioned concerning changes in health
status and changes in or additions to concomitant medications since the Screening Visit.
Qualified study personnel took vital signs and assessed the subject’s scalp for any signs of
irritation or dermatological conditions that would disqualify the subject from study
participation. The following procedures were completed in successive order: repeat
global digital images (for documentation of hair loss), target site area identification, hair
clipping, tattooing, macro imaging, randomization, and test product, instructions and
diary dispensation. All global digital images were taken prior to the hair
clipping/tattooing.
Hair Clipping:
A circle, approximately 1 inch in diameter, positioned in the vertex portion of the scalp,
was identified as the site for hair clipping. Within this site was the target area for the hair
density evaluation. The target area was located in the vertex portion of the subject’s
scalp and had the presence of some miniaturized hairs. A template was provided to the
investigator for identifying the area for hair clipping. Once the hair had been clipped,
trained study personnel used a professional tattooing machine to apply a permanent ink
dot, approximately the size of a period (.) in the center of the circle. The tattoo was used
as a guide for placing the template on the scalp surface at subsequent visits for the hair
clipping and macro images for hair density evaluation (see below).
Imaging and Hair Densities Procedures:
1. Image acquisition
The subject sat in a chair and was properly placed into the stereotactic apparatus. The
digital images were standardized for lighting, camera angle, and position of subject’s
head in each digital image to achieve similar camera angle and relative image size. For
macro digital images a template was placed on the lenses for precise and consistent
alignment on the tattoo. The template was approximately a 7 cm2 area circle with a
diameter of 2.96 cm. A 10 mm scale divided in 0.1 mm increments was etched into the
template for calibration purposes during the Hair Density evaluations. The images were
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recorded on compact flash cards. During the subject’s visit the images were previewed
to see if images were acceptable. If images were unacceptable they were retaken.
After the subject’s visit was complete, the images were printed and signed by the
investigator and uploaded to a designated site for image archiving.
Subjects were randomized into two groups: LaserComb or placebo (sham device).
Diaries to document subject use were distributed.
2. Image Management Software Overview
Canfield Mirror DPS 6.1.1 software system was utilized for image management. Macro
images were imported into a blinded subject file labeled by subject number. Mirror DPS
displayed the image and provided a means to mark each individual hair. Each hair was
“clicked” and a running count was displayed at the bottom of the software window. Only
terminal hairs were counted. Archives of the counted hairs were maintained in the subject
file. Images can be displayed side by side.
3. Image Analysis and Management
The software’s database functionality allows subjects to be identified by number while
the advanced multiple criteria searches facilitate quick retrieval of information. In
addition, the subject’s chart view allowed a look at all of a subject’s images on one
screen with scalable thumbnails. Blinded subject records containing hair density
measurements were forwarded to data management for inclusion in the study database.
3.3 Visit 3 (Week 8) and Visit 4 (Week 16)
Subjects returned to the study site and were questioned concerning potential adverse
events and changes in or additions to concomitant medications since the last visit.
Continuance criteria were reviewed. Diaries were collected and reviewed. Qualified study
personnel took vital signs and evaluated the scalp of each subject for local dermatitis and
other concurrent scalp conditions.
Global images were taken using a digital camera. These digital images were taken prior
to hair clipping, tattoo (if needed), and preparation for macro images.
Imaging:
To document any evidence of initial hair reverse miniaturization and re-growth, digital
images were taken. If the global digital images were non-evaluable, they were repeated
within two weeks of this visit. All imaging was conducted in the same order and with the
same methods as at the Screening and Baseline Visits.
Hair Clipping/Macro imaging:
Following global imaging, the designated hair site was clipped and prepared and the
tattoo was reapplied if necessary. Macro images were taken of the target site within the
clipped area following the site preparation.
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Diaries for collecting subject usage habits were distributed. Subjects were asked what
treatment they thought they had received and why. Subjects were instructed as to how to
complete the questionnaire; however there was no assistance available to the subject in
answering the questionnaire. Hair density evaluations were performed.
3.4 Visit 5 (Week 26) or Early Termination
Subjects returned to the study site and were questioned concerning potential adverse
events and changes in or additions to concomitant medications since the last visit.
Continuance criteria were reviewed. Diaries were collected and reviewed. Qualified study
personnel took vital signs and evaluated the scalp of each subject for local dermatitis.
Imaging:
Global images were taken using a digital camera. These images were taken prior to hair
clipping, tattoo (if needed), and preparation for macro images.
Hair Clipping/Macro images:
The designated hair site was clipped and prepared. The tattoo was reapplied if necessary.
Macro images were taken of the target site within the clipped hair site following the
procedures done at Baseline.
Subjects were asked what treatment they thought they had received and why. Subjects
were asked to comment on the clarity of the usage instructions. Subjects were instructed
to complete the Subject Questionnaire Subjects were instructed as to how to complete
the questionnaire; however there was no assistance available to the subject in answering
the questionnaire. Investigator’s were asked to evaluate the subject’s hair growth looking
at the baseline and Week 5 (or Early Termination) visit global images and graded the hair
growth on a four-point scale. Hair Density evaluations were performed
If at any time during the study, a subject discontinued participation or was discontinued
by the investigator, all the procedures and documentation identified at the Week 26 visit
were performed.
4. Pre-Specified Study Endpoints
4.1 Primary Effectiveness Endpoint
The primary effectiveness endpoint is the change in non-vellus terminal hair density
(hairs/cm2) in the target region between Baseline and Endpoint (Week 26 or final visit),
utilizing macro images.
4.2 Secondary Effectiveness Endpoints
• Subject’s static assessment of the condition of the hair at each follow-up visit
without referring to any images taken. (Question in Subject Questionnaire. “How
would you rate your overall hair regrowth?”). The last available visit was used.
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• Investigator’s global assessment of hair growth.
• Additional ten questions in the Subject Questionnaire. The last available visit was
used for each.
4.3 Safety Endpoints
All adverse events and vital signs.
5.0 Description of Statistical Methods
5.1 Sample Size Calculations
Based on prior data with the LaserComb and with the drug minoxidil, the standard
deviation of change from baseline in terminal hair density was assumed to be 30
hairs/cm2. Based on this estimate, 93 subjects randomized 2:1 (62 in the LaserComb
group and 31 in the placebo group) would provide 85% power to detect a difference of 20
hairs/cm2. To allow for a 20% drop out rate, 116 subjects were to be enrolled.
5.2 Baseline Comparisons
Statistical comparisons were made between treatment groups for all baseline
demographic variables. Continuous variables were compared with two sample t tests,
dichotomous variables by Pearson’s chi square, and ordinal variables by the Cochran-
Mantel-Haenszel procedure after assigning uniform scores (1, 2, 3, etc) to the ordered
categories.
5.3 Datasets
The primary analysis of effectiveness was performed on all randomized subjects who had
a post-baseline hair density. In addition, an intent-to-treat analysis was performed in
which a change from baseline in hair density was imputed to be zero for all subjects who
did not have a post-baseline hair density, although this was not specified in the protocol.
All randomized subjects who used the study device at least once were included in
analyses of safety.
5.4 Primary Effectiveness Analysis
The primary analysis of effectiveness was an analysis of covariance which included the
effects of treatment group, study center, age (as a continuous variable), and Fitzpatrick
Skin Type Classification (as a categorical variable with four levels). The effect of
treatment group was tested as a two-sided test at the 5% level of significance.
Additional secondary analyses were performed on the primary variable. The
comparability of study centers was assessed by adding the center-by-treatment interaction
to the primary analysis model. In addition, the interactions of treatment group with each
of the other covariates in the primary analysis were also tested. Although not specified in
the protocol, an intent-to-treat analysis was performed in which a change from baseline in
hair density was imputed to be zero for all subjects who did not have a post-baseline hair
density.
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5.5 Secondary Effectiveness Analyses
Each of the secondary variables is an ordinal variable with either four or five ordered
categories of response. The Cochran-Mantel-Haenszel procedure was used to analyze
each of these variables, stratified by study center. Uniform scores (1, 2, 3, etc.) were
assigned to the ordered categories. Each secondary analysis was performed as a two-
sided test at a nominal significance level of 5%.
The amount of agreement between actual device and perceived device was assessed by a
kappa statistic, which is the amount of agreement above that due to chance alone. This
statistic is of the form (Io – Ie)/(1 – Ie), where Io is the observed agreement (proportion of
subjects who were correct) and Ie is the expected agreement (proportion of subjects
demonstrating agreement under complete independence).
5.6 Analyses of Safety
The protocol stated that the MedDRA coding dictionary would be used for coding
adverse events, however, the Costart dictionary was used. Adverse events are
summarized as the number and percentage of subjects reporting each event. Statistical
comparisons were made between treatment groups using Fisher’s Exact Test. Adverse
events rated as possibly, probably, and definitely related to the study device are
summarized. Adverse events are also summarized by severity and by action taken to
treat them.
Vital signs were summarized by their means at baseline and change from baseline to each
scheduled visit. Comparisons between treatment groups were made by two sample t
tests.
6.0 Results
6.1 Subject Accounting
A total of 123 subjects were enrolled between September 24, 2004 and February 21, 2005
at four study sites. The number of subjects enrolled by study site and treatment group is
summarized in Table 2.
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Table 2: Number Subjects Treated by Investigator
Site Number Investigator Name Subjects Treated
LaserComb Placebo Total
1 Irwin Kantor, M.D. 20 10 30
2 Elyse Rafal, M.D. 11 6 17
3 Harlan Bieley, M.D. 17 9 26
4 Toni Funicella, M.D. 34 16 50
Total 82 41 123
Subject accounting is summarized in Table 3. Of the 123 subjects enrolled, 110 (89.4%)
completed the study. Seven subjects were terminated by the sponsor due to violations of
baseline entry criteria (6 in the LaserComb group and 1 in the placebo group, p=0.42).
Each of these subjects was terminated at the Week 8 visit because the site location of the
target area for hair density evaluation was outside the zone with miniaturized hairs. The
decision to terminate these subjects was done by the sponsor without knowledge of
treatment assignment. One subject was terminated due to noncompliance with study
visits. One subject was lost to follow-up. Four subjects withdrew consent for other
reasons. Among these four subjects, the two subjects in the placebo group had an early
termination visit (at 71 and 112 days) at which they had a hair density measurement done.
Hence, the ten subjects in the LaserComb group who terminated prematurely are not
included in the primary analysis of effectiveness, and only one of the three subjects in the
placebo group who terminated prematurely is not included.
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Table 3: – Subject Accounting
LaserComb Placebo Total
Number Randomized 82 41 123
Number (%) Completed 72 (87.8%) 38 (92.7%) 110 (89.4%)
Number (%) Discontinued 10 (12.2%) 3 (7.3%) 13 (10.6%)
Did not meet baseline criteria 6 1 7
Did not meet continuation criteria 1 0 1
Adverse Event 0 0 0
Withdrew consent 2 2 4
Lost to follow-up 1 0 1
Number (%) Completed 8 Week Visit 80 (97.6%) 40 (97.6%) 120 (97.6%)
Days from baseline visit
Mean (range) 56.6 (52, 79) 56.2 (52, 67) 56.4 (52, 79)
Median 56 56 56
Number (%) Completed 16 Week Visit 72 (87.8%) 38 (92.7%) 110 (89.4%)
Days from baseline visit
Mean (range) 113.3(109,127) 112.8(111-122) 113.1(109,127)
Median 112 112 112
Number (%) Completed 26 Week Visit 72 (87.8%) 38 (92.7%) 110 (89.4%)
Days from baseline visit
Mean (range) 182.0(175,197) 182.0(179,190) 182.0(175,197)
Median 182 182 182
Number (%) Included in Primary
Analysis
72 (87.8%) 40 (97.6%) 112 (91.1%)
6.2 Baseline Assessments
Table 4 summarizes the baseline demographic variables. The mean age was just under
47 years, and 90% of the subjects were white. As seen in Table 4, the baseline
demographics were comparable between the two subject cohorts.
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Table 4: Baseline Demographic Summary
LaserComb
(N=82)
Placebo
(N=41)
P-Value
Age
Mean ± Std 46.4 ± 7.3 47.1 ± 7.9 0.61
Range 30, 60 31, 59
Race
White, Non-Hispanic 74 (90.2%) 37 (90.2%) 1.01
Hispanic 5 (6.1%) 4 (9.8%)
American Indian or Alaskan Native 2 (2.4%) 0 (0%)
Other 1 (1.2%) 0 (0%)
Norwood-Hamilton Classification
II 2 (2.4%) 1 (2.4%) 0.46
III 29 (35.4%) 13 (31.7%)
IV 28 (34.1%) 12 (29.3%)
V 23 (28.0%) 15 (36.6%)
Fitzpatrick Skin Type Classification
I 2 (2.4%) 2 (4.9%) 0.07
II 9 (11.0%) 8 (19.5%)
III 43 (52.4%) 22 (53.7%)
IV 28 (34.2%) 9 (22.0%)
1 White vs. non-white
Table 5 summarizes medical history by body system. Subjects in the two treatment
groups had comparable medical history.
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Table 5: Medical History Summary
System LaserComb
(N=82)
n (%)
Placebo
(N=41)
n (%)
P-Value
HEENT 19 (23.2%) 10 (24.4%) 1.0
Cardiovascular 28 (34.2%) 11 (26.8%) 0.41
Respiratory 6 (7.3%) 4 (9.8%) 0.73
Gastrointestinal 15 (18.3%) 5 (12.2%) 0.39
Renal 1 (1.2%) 3 (7.3%) 0.11
Hepatic 3 (3.7%) 0 (0%) 0.55
Genitourinary 5 (6.1%) 2 (4.9%) 1.0
Reproductive 0 (0%) 2 (4.9%) 0.11
Endocrine 5 (6.1%) 2 (4.9%) 1.0
Hematologic 2 (2.4%) 0 (0%) 0.55
Lymphatic 0 (0%) 0 (0%) 1.0
Neurologic 10 (12.2%) 5 (12.2%) 1.0
Psychiatric 6 (7.3%) 2 (4.9%) 0.72
Immunologic 36 (43.9%) 15 (36.6%) 0.44
Dermatologic 8 (9.8%) 5 (12.2%) 0.76
Musculoskeletal 30 (36.6%) 17 (41.5%) 0.60
Other 2 (2.5%) 2 (5.1%) 0.60
Two subjects in the LaserComb treatment group (2.4%) had a device malfunction, while
no subject in the placebo group did.
6.3 Primary Effectiveness Analysis
The results of the primary analysis are summarized in Table 6, and shown graphically in
Figure 1. The individual results for each subject are listed in Appendix 1. The baseline
and change from baseline are first summarized with simple summary statistics. The
baseline means are nearly identical. The adjusted mean change from baseline is based on
the model which accounts for study center, subject’s age, and Fitzpatrick Skin Type
Classification. Subjects in the LaserComb group had a mean increase in hair density of
18.8 hairs/cm2, while subjects in the placebo group had a mean decrease of 10.6
hairs/cm2 (p<0.0001). Hence, subjects in the LaserComb treatment group had
significantly greater increase in mean hair density than subjects in the placebo group.
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Table 6: Mean Baseline and Change From Baseline to 26 Weeks in Terminal Hair
Density1 (hairs/cm2)
LaserComb
(N=72)
Placebo
(N=40)
Baseline
Mean ± Std 124.1 ± 52.1 124.7 ± 54.3
Range 21.6, 252.1 25.5, 281.4
Change from baseline
Mean ± Std 16.3 ± 14.6 -12.3 ± 24.5
Range -56.0, 52.2 -145.1, 7.6
Adjusted mean2 18.8 -10.6
Difference (95% CI) 29.4 (22.0, 36.8)
P-Value <0.0001
1 The last value was carried forward for subjects who terminated prematurely
2 Adjusted for study center, subject’s age, and skin type
Table 6a: Mean Baseline and Change From Baseline to 26 Weeks in Terminal Hair
Density1 (hairs/cm2) – Male and Female Subjects
LaserComb
(N=81)
Placebo
(N=47)
Baseline
Mean ± Std 124.5 ± 49.7 123.7 ± 53.1
Range 21.6, 252.1 25.5, 281.4
Change from baseline
Mean ± Std 17.5 ± 14.8 -11.5 ± 22.7
Range -56.0, 53.5 -145.1, 7.6
Adjusted mean2 20.6 -8.7
Difference (95% CI) 29.3 (22.8, 35.8)
P-Value <0.0001
1 The last value was carried forward for subjects who terminated prematurely
2 Adjusted for sex
To demonstrate the individual subject changes from baseline in terminal hair density,
Table 7 summarizes the individual subject results in six categories. Only two subjects in
the LaserComb group (2.8%) had a decrease in hair density = 5 hairs/cm2, while 26
subjects in the placebo group (65.0%) had a similar decrease. Moreover, 67 subjects in
the LaserComb group (93.1%) had at least some increase in hair growth compared to
only 5 subjects in the placebo group (12.5%). Finally, 62 subjects in the LaserComb
group (86.1%) had an increase in hair density greater than 5 hairs/cm2, while only two
subjects in the placebo (5.0%) group had such an increase. These results are also shown
graphically in Figures 2 and 3.
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Table 7: Categorical Changes From Baseline to 26 Weeks in Terminal Hair Density1
(hairs /cm2)
Change in Hair
Density/cm2
LaserComb
(N=72)
n (%)
Placebo
(N=40)
n (%)
= -20 1 (1.4%) 7 (17.5%)
>-20 to -5 1 (1.4%) 19 (47.5%)
>-5 to 0 3 (4.2%) 9 (22.5%)
>0 to 5 5 (6.9%) 3 (7.5%)
>5 to 20 34 (47.2%) 2 (5.0%)
>20 28 (38.9%) 0 (0%)
1 The last value was carried forward for subjects who terminated prematurely
Table 7a: Categorical Changes From Baseline to 26 Weeks in Terminal Hair
Density1 (hairs /cm2) – Male and Female Subjects
Change in Hair
Density/cm2
LaserComb
(N=81)
n (%)
Placebo
(N=47)
n (%)
= -20 1 (1.2%) 7 (14.9%)
>-20 to -5 1 (1.2%) 23 (48.9%)
>-5 to 0 3 (3.7%) 12 (25.5%)
>0 to 5 5 (6.2%) 3 (6.4%)
>5 to 20 39 (48.2%) 2 (4.3%)
>20 32 (39.5%) 0 (0%)
1 The last value was carried forward for subjects who terminated prematurely
The two subjects with the greatest decreases in Hair Density (Subject 04-039 in the
placebo group with -145 hairs/cm2 and Subject 01-039 with -56 hairs/cm2) appeared to be
outliers in the statistical analysis. The residual standard deviation from the analysis of
variance was 18.6 hairs/cm2 and these subjects had residuals of -128.0 (Subject 04-039)
and -75.8 (Subject 01-039). To assess the impact of these subjects on the analysis, they
were removed, and the results are shown in Table 8. Removal of these subjects reduced
the residual standard deviation from 18.6 to 11.2 hairs/cm2, however, the impact on the
final results was negligible.
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Table 8: Mean Baseline and Change From Baseline to 26 Weeks in Terminal Hair
Density1 (hairs /cm2) – Two Outliers Excluded2
LaserComb
(N=71)
Placebo
(N=39)
Baseline
Mean ± Std 122.9 ± 51.4 120.7 ± 48.6
Range 21.6, 252.1 25.5, 225.4
Change from baseline
Mean ± Std 17.3 ± 11.9 -8.9 ± 11.7
Range -6.4, 52.2 -54.7, 7.6
Adjusted mean3 19.8 -7.6
Difference (95% CI) 27.4 (22.9, 31.9)
P-Value <0.0001
1 The last value was carried forward for subjects who terminated prematurely
2 Subject 04-039 in placebo group (residual = -128.0) and Subject 01-039 in LaserComb group (residual = 75.8)
3 Adjusted for study center, subject’s age, and skin type
Although not specified in the protocol, an intent-to-treat analysis was performed which
included all randomized subjects. The change from baseline in terminal hair density for
the 11 subjects excluded from the primary analysis (10 in the LaserComb group and one
in the placebo group) was imputed to be zero. The results of this analysis are shown in
Table 9. The difference in adjusted means decreased from 29.4 hairs/cm2 to 26.9
hairs/cm2, however, the difference remained highly statistically significant (p<0.0001).
Table 9: Change From Baseline to 26 Weeks in Terminal Hair Density1 (hairs /cm2)
A Change From Baseline of Zero Was Imputed For Subjects With No Final Hair
Density
LaserComb
(N=82)
Placebo
(N=41)
Change from baseline
Mean ± Std 14.3 ± 14.7 -12.0 ± 24.2
Range -56.0, 52.2 -145.1, 7.6
Adjusted mean2 16.5 -10.4
Difference (95% CI) 26.9 (19.7, 34.1)
P-Value <0.0001
1 The last value was carried forward for subjects who terminated prematurely
2 Adjusted for study center, subject’s age, and skin type
The comparability of study centers was assessed by adding the interaction between study
center and treatment group to the primary model. To avoid the impact of the two outliers
discussed above, these two subjects were removed from the analysis, and from all
subsequent subgroup analyses. The resulting interaction had a p-value of 0.033.
The results are shown by study center in Table 10. Subjects treated with the LaserComb
had a mean increase in hair density at each of the four study sites (12.4 to 23.7 hairs/cm2),
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while those treated with the placebo exhibited a mean decrease at each of the four sites
(0.5 to 17.7 hairs/cm2), resulting in the range of mean differences between treatment
groups between 12.9 and 32.8 hairs/cm2. Although the interaction achieved nominal
significance of p<0.05, the increase in hair density in the LaserComb group over that in
the placebo group was substantial at each study site. Hence, the results clearly indicate
that the device was effective at each study site, with the only differences being in the
magnitude of the effect.
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Table 10: Mean Baseline and Change From Baseline to 26 Weeks in Terminal Hair
Density1 (hairs /cm2) by Study Site
Site No. LaserComb Placebo
Baseline Change From
Baseline
Baseline Change From
Baseline
1
N 14 14 9 9
Mean ± Std 104.0 ± 47.2 22.2 ± 14.5 101.6 ± 44.6 -7.9 ± 8.3
Range 31.8, 201.2 -1.3, 52.2 39.5, 161.7 -20.4, 5.1
Adjusted
Change2
N/A 22.5 N/A -6.3
Difference in
mean changes
28.8
2
N 9 9 6 6
Mean ± Std 119.0 ± 48.3 10.7 ± 6.0 93.6 ± 38.2 -0.6 ± 3.3
Range 39.5, 187.2 2.3, 19.1 25.5, 132.4 -5.1, 3.8
Adjusted
Change2
N/A 12.4 N/A -0.5
Difference in
mean changes
12.9
3
N 14 14 9 9
Mean ± Std 144.9 ± 45.4 21.3 ± 11.6 118.4 ± 39.1 -3.1 ± 6.9
Range 61.1, 215.2 10.2, 47.1 38.2, 163.0 -16.6, 7.6
Adjusted
Change2
N/A 23.7 N/A -1.4
Difference in
mean changes
25.1
4
N 34 34 15 15
Mean ± Std 122.7 ± 54.6 15.4 ± 11.1 144.3 ± 52.3 -16.2 ± 13.9
Range 21.6, 252.1 -6.4, 38.2 29.3, 225.4 -54.7, -1.3
Adjusted
Change2
N/A 15.1 N/A -17.7
Difference in
mean changes
32.8
1 The last value was carried forward for subjects who terminated prematurely. Subjects 01-039 and 04-039
excluded.
2 Adjusted for subject’s age and skin type
The effects of the additional two covariates included in the primary analysis on change in
hair density were assessed by adding their interactions with treatment group to the
primary analysis model. The interaction with Fitzpatrick Skin Type Classification had a
p-value of 0.44. The interaction with age was assessed by first grouping the ages into
three groups of approximately equal size, resulting in an interaction with this
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classification and treatment group of p=0.08. The resulting subgroup analyses are shown
in Tables 11 and 12. The benefit of the LaserComb is seen in all subgroups.
Table 11: Mean Change From Baseline to 26 Weeks in Terminal Hair Density1
(hairs /cm2) by Fitzpatrick Skin Type
Skin Type LaserComb Placebo
N Mean Change2 N Mean Change2
I 2 16.5 2 2.9
II 8 21.2 8 -8.4
III 36 19.8 20 -6.0
IV 25 16.4 9 -14.9
1 The last value was carried forward for subjects who terminated prematurely. Subjects 01-039 and 04-039
excluded.
2 Adjusted for site and subject’s age
Table 12: Mean Change From Baseline to 26 Weeks in Terminal Hair Density1
(hairs /cm2) by Age Group
Age Group LaserComb Placebo
N Mean Change2 N Mean Change2
30 – 43 22 24.0 13 -8.4
44 – 50 30 19.5 10 -10.5
51 – 60 19 14.9 16 -5.5
1 The last value was carried forward for subjects who terminated prematurely. Subjects 01-039 and 04-039
excluded.
2 Adjusted for site and skin type
As stated in the methods section (Section 1.5), the protocol was originally designed for
both males and females and was subsequently amended to only include males at the
request of FDA. The results of the 16 female subjects who were randomized prior to this
amendment are shown in Table 13 for informational purposes only.
Table 13: Mean Baseline and Change From Baseline to 26 Weeks in Terminal Hair
Density1 (hairs /cm2) Among Female Subjects
LaserComb
(N=9)
Placebo
(N=7)
Baseline
Mean ± Std 127.6 ± 24.7 117.9 ± 49.0
Range 89.1, 165.5 40.7, 189.7
Change from baseline
Mean ± Std 26.7 ± 13.6 -7.3 ± 6.9
Range 12.7, 53.5 -15.8, 0
These results, along with the additional female subjects to be treated, will be included in
a future submission when the study has completed. As seen in Table 13, the results in
this small number of subjects are comparable to those in males.
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6.4 Secondary Effectiveness Analyses
Secondary effectiveness variables included the subject’s assessment of overall hair
regrowth, the investigator’s global assessment of hair growth, and ten additional
questions in the Subject Questionnaire.
The subject’s assessment of overall hair regrowth is summarized in Table 14 by
scheduled visit, and the last assessment for each subject is included in the listing in
Appendix 1. Subjects who terminated prematurely had their last value carried forward to
each subsequent visit. As seen in this table, the p-value comparing treatment groups
decreased over time, achieving nominal statistical significance (p=0.010) at the last visit.
Hence, subjects in the LaserComb group perceived significantly greater improvement
over those in the placebo group in hair regrowth at the end of the study. The four
response categories were coded from 1 (No Growth) to 4 (Dense Growth) and the means
of these responses are presented graphically in Figure 4.
Table 14: Subjects’ Assessment of Overall Hair Regrowth – Last Observation
Carried Forward
LaserComb
n (%)
Placebo
n (%)
P-Value
Week 8
N 76 38
No Growth 36 (47.4%) 18 (47.4%) 0.50
Minimal Growth 27 (35.5%) 17 (44.7%)
Moderate Growth 13 (17.1%) 3 (7.9%)
Dense Growth 0 (0%) 0 (0%)
Week 16
N 76 39
No Growth 31 (40.8%) 18 (46.2%) 0.16
Minimal Growth 32 (42.1%) 19 (48.7%)
Moderate Growth 12 (15.8%) 2 (5.1%)
Dense Growth 1 (1.3%) 0 (0%)
Week 26
N 76 39
No Growth 28 (36.8%) 21 (53.9%) 0.010
Minimal Growth 30 (39.5%) 16 (41.0%)
Moderate Growth 17 (22.4%) 2 (5.1%)
Dense Growth 1 (1.3%) 0 (0%)
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The results of the investigator’s global assessment of hair growth are presented in Table
15. There was no difference between treatment groups in this assessment (p=0.45).
Table 15: Investigator’s Global Assessment of Hair Growth at 26 Weeks
Assessment LaserComb
(N=72)
n (%)
Placebo
(N=38)
n (%)
P-Value
No growth 46 (63.9%) 22 (57.9%) 0.45
Minimal growth 18 (25.0%) 10 (26.3%)
Moderate growth 7 (9.7%) 5 (13.2%)
Dense growth 1 (1.4%) 1 (2.6%)
The agreement between the investigator’s subjective global assessments with the
objective hair density measurements was assessed by comparing the median changes
from baseline in terminal hair density within each treatment group and category of
response (Table 16). Medians are used rather than means to lessen the impact of the
large decreases. No relationship is seen between median changes and investigator
assessment among subjects in the LaserComb group and very little relationship is seen
among subjects in the placebo group. However, substantial differences are seen between
treatment groups within each assessment category. These results bring to question the
validity of the investigators’ subjective assessments of hair growth due to their lack of
any agreement with actual hair growth.
Table 16: Median Change From Baseline in Terminal Hair Density (hairs /cm2) by
Investigator’s Global Assessment of Hair Growth at 26 Weeks
Assessment LaserComb
Median Change (N)
Placebo
Median Change (N)
Difference in
Medians
No growth 14.6 (46) -7.0 (22) 21.6
Minimal growth 19.1 (18) -6.4 (10) 25.5
Moderate growth 14.0 (7) -5.1 (5) 19.1
Dense growth 34.4 (1) 0.0 (1) 34.4
Results from the last available visit for each of the ten additional items in the Subject
Questionnaire are presented in Tables 17 – 28. Three of the items (reduced dandruff,
return to natural color, and scalp irritation) were not analyzed statistically due to the high
proportions of subjects responding not applicable. Among the remaining seven items,
five achieved nominal statistical significance (p<0.05), indicating significantly better
assessments among subjects in the LaserComb group than among those in the placebo.
The last two items that did not achieve nominal statistical significance (p<0.05) did
demonstrate a better overall assessment among subjects in the LaserComb group than
among those in the placebo group. As with the Subjects’ Assessment of Overall Hair
Regrowth, each of these items was coded from 1 to either 4 or 5 and the means are shown
by visit in Figures 5 – 11. As seen in each of these figures, the mean responses for
subjects in the LaserComb treatment group were always numerically superior to those in
the placebo group.
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Table 17: Subjects’ Assessment of Rate of Hair Loss Slowed At 26 Weeks
Last Observation Carried Forward
LaserComb
n (%)
(N=75)
Placebo
n (%)
(N=39)
P-Value
Not at all 30 (40.0%) 25 (64.1%) 0.0211
Slight 26 (34.7%) 10 (25.6%)
Moderate 12 (16.0%) 2 (5.1%)
Good 3 (4.0%) 1 (2.6%)
Greatly 4 (5.3%) 1 (2.6%)
1 Subjects in the LaserComb group reported a significantly better assessment than those in the placebo
group
Table 18: Subjects’ Assessment of Dandruff Reduced At 26 Weeks
Last Observation Carried Forward
LaserComb
n (%)
(N=75)
Placebo
n (%)
(N=39)
P-Value
N/A 55 (73.3%) 31 (79.5%) *
Not at all 5 (6.7%) 4 (10.3%)
Slight 4 (5.3%) 3 (7.7%)
Moderate 3 (4.0%) 1 (2.6%)
Good 7 (9.3%) 0 (0%)
Greatly 1 (1.3%) 0 (0%)
* Too few data
Table 19: Subjects’ Assessment of Better Scalp Health At 26 Weeks
Last Observation Carried Forward
LaserComb
n (%)
(N=76)
Placebo
n (%)
(N=39)
P-Value
Not at all 33 (43.4%) 20 (52.6%) 0.0331
Slight 23 (30.3%) 15 (39.5%)
Moderate 11 (14.5%) 3 (7.9%)
Good 8 (10.5%) 0 (0%)
Greatly 1 (1.3%) 0 (0%)
1 Subjects in the LaserComb group reported a significantly better assessment than those in the placebo
group
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Table 20: Subjects’ Assessment of Hair Feeling Thicker At 26 Weeks
Last Observation Carried Forward
LaserComb
n (%)
(N=76)
Placebo
n (%)
(N=39)
P-Value
Not at all 33 (43.4%) 24 (61.5%) 0.0341
Slight 24 (31.6%) 11 (28.2%)
Moderate 12 (15.8%) 2 (5.1%)
Good 5 (6.6%) 2 (5.1%)
Greatly 2 (2.6%) 0 (0%)
1 Subjects in the LaserComb group reported a significantly better assessment than those in the placebo
group
Table 21: Subjects’ Assessment of More Shine to Hair At 26 Weeks
Last Observation Carried Forward
LaserComb
n (%)
(N=76)
Placebo
n (%)
(N=39)
P-Value
Not at all 35 (46.1%) 22 (56.4%) 0.0421
Slight 21 (27.6%) 14 (35.9%)
Moderate 12 (15.8%) 2 (5.1%)
Good 6 (7.9%) 1 (2.6%)
Greatly 2 (2.6%) 0 (0%)
1 Subjects in the LaserComb group reported a significantly better assessment than those in the placebo
group
Table 22: Subjects’ Assessment of Hair Returned to Natural Color At 26 Weeks
Last Observation Carried Forward
LaserComb
n (%)
(N=76)
Placebo
n (%)
(N=39)
P-Value
N/A 45 (59.2%) 28 (71.8%) *
Not at all 17 (22.4%) 7 (18.0%)
Slight 9 (11.8%) 4 (10.3%)
Moderate 3 (4.0%) 0 (0%)
Good 1 (1.3%) 0 (0%)
Greatly 1 (1.3%) 0 (0%)
* Too few data
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Table 23: Subjects’ Assessment of Rate of Hair Growing Faster At 26 Weeks
Last Observation Carried Forward
LaserComb
n (%)
(N=76)
Placebo
n (%)
(N=39)
P-Value
Not at all 40 (52.6%) 23 (59.0%) 0.16
Slight 19 (25.0%) 12 (30.8%)
Moderate 10 (13.2%) 3 (7.7%)
Good 6 (7.9%) 1 (2.6%)
Greatly 1 (1.3%) 0 (0%)
Table 24: Subjects’ Assessment of Rate of Scalp Irritation Reduced At 26 Weeks
Last Observation Carried Forward
LaserComb
n (%)
(N=74)
Placebo
n (%)
(N=39)
P-Value
N/A 54 (73.0%) 34 (87.2%) *
Not at all 6 (8.1%) 3 (7.7%)
Slight 10 (13.5%) 2 (5.1%)
Moderate 1 (1.4%) 0 (0%)
Good 2 (2.7%) 0 (0%)
Greatly 1 (1.4%) 0 (0%)
* Too few data
Table 25: Subjects’ Assessment of Rate of Hair More Manageable At 26 Weeks
Last Observation Carried Forward
LaserComb
n (%)
(N=76)
Placebo
n (%)
(N=39)
P-Value
Not at all 37 (48.7%) 24 (63.2%) 0.10
Slight 25 (32.9%) 10 (26.3%)
Moderate 8 (10.5%) 3 (7.9%)
Good 5 (6.6%) 1 (2.6%)
Greatly 1 (1.3%) 0 (0%)
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Table 26: Subjects’ Assessment of Rate of Overall Hair Improvement At 26 Weeks
Last Observation Carried Forward
LaserComb
n (%)
(N=76)
Placebo
n (%)
(N=39)
P-Value
None 28 (36.8%) 19 (48.7%) 0.0381
Slight 31 (40.8%) 17 (43.6%)
Moderate 10 (13.2%) 2 (5.1%)
Good 4 (5.3%) 1 (2.6%)
Greatly 3 (4.0%) 0 (0%)
1 Subjects in the LaserComb group reported a significantly better assessment than those in the placebo
group
Subjects were asked to guess which device they believed they had been using at each
scheduled visit (Table 27). The amount of agreement between actual device and
perceived device was assessed by a kappa statistic, which is the amount of agreement
above that due to chance alone. The value of this statistic is zero for no agreement and
1.0 for perfect agreement. As seen in this table, the agreement was not very good,
indicating blinding was maintained in the study.
Table 27: Subject’s Guess of Which Device They Had
Study
Week
Actual Device Subject’s Guess Kappa
LaserComb Placebo
8 LaserComb n (%) 37 (49.3%) 38 (50.7%) 0.24
Placebo n (%) 8 (20.5%) 31 (79.5%)
16 LaserComb n (%) 35 (48.6%) 37 (51.4%) 0.21
Placebo n (%) 9 (23.7%) 29 (76.3%)
26 LaserComb n (%) 30 (41.7%) 42 (58.3%) 0.24
Placebo n (%) 5 (12.5%) 35 (87.5%)
6.5 Analyses of Safety
One or more adverse events were reported in 19/82 (23.2%) subjects in the LaserComb
group and 11/41 (26.8%) subjects in the placebo group (p=0.66). There was no serious
adverse event reported in this study. The only adverse events reported by greater than
two subjects in the LaserComb group were cold (n=3), paresthesia (n=4), and urticaria
(n=4). The four cases of paresthesia in the LaserComb group were considered device-
related, three possibly and one probably related to the device. The statistical comparison
of paresthesia between treatment groups shows p=0.30. Four of the five cases of urticaria
were considered device-related, the case in the placebo group was possibly device-related
and the four subjects in the LaserComb group rated it as not related (n=1), possibly
related (n=1), and probably related (n=2). The statistical comparison of device-related
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urticaria between treatment groups shows p=1.0. All cases of paresthesia and urticaria
were rated as mild, and none required treatment. In three of the four subjects reporting
paresthesia, the onset was within the first two days of treatment, and was on the 12th day
for the fourth subject. In two of the subjects it lasted only one or two days, and in two
subjects it was persistent. Table 28 summarizes the numbers of subjects reporting each
adverse event by treatment group. The rates were comparable between the two treatment
groups.
Table 28: Summary of Adverse Events
Adverse Event LaserComb
(N=82)
n (%)
Placebo
(N=41)
n (%)
P-Value
Subjects with at least one AE 19 (23.2%) 11 (26.8%) 0.66
Asthma 1 (1.2%) 0 (0%) 1.0
Benign prostatic hyperplasia 0 (0%) 1 (2.4%) 0.33
Bronchitis 1 (1.2%) 0 (0%) 1.0
Cold 3 (3.7%) 2 (4.9%) 1.0
Dental infection 1 (1.2%) 1 (2.4%) 1.0
Depression 0 (0%) 1 (2.4%) 0.33
Dizziness 0 (0%) 1 (2.4%) 0.33
Dry skin 2 (2.4%) 1 (2.4%) 1.0
Dryness of scalp 0 (0%) 1 (2.4%) 0.33
Fever 0 (0%) 1 (2.4%) 0.33
Fracture-foot 1 (1.2%) 0 (0%) 1.0
Hoarseness 1 (1.2%) 0 (0%) 1.0
Hypercholesterolemia 0 (0%) 1 (2.4%) 0.33
Hypertension 0 (0%) 1 (2.4%) 0.33
Hypertonia-neck 0 (0%) 1 (2.4%) 0.33
Infection – urinary tract 0 (0%) 1 (2.4%) 0.33
Influenza 2 (2.4%) 0 (0%) 0.55
Laceration 2 (2.4%) 1 (2.4%) 1.0
Migraine 0 (0%) 1 (2.4%) 0.33
Nausea 0 (0%) 1 (2.4%) 0.33
Dandruff 0 (0%) 1 (2.4%) 0.33
Paresthesia 4 (4.9%) 0 (0%) 0.30
Pruritis 1 (1.2%) 0 (0%) 1.0
Rash 1 (1.2%) 0 (0%) 1.0
Skin disorder – scabs 1 (1.2%) 0 (0%) 1.0
Skin irritation 1 (1.2%) 0 (0%) 1.0
Sleep apnea 1 (1.2%) 0 (0%) 1.0
Urinary retention 0 (0%) 1 (2.4%) 0.33
Urticaria 4 (4.9%) 1 (2.4%) 0.66
Vasodilatation 1 (1.2%) 0 (0%) 1.0
Vasodilatation – scalp 1 (1.2%) 0 (0%) 1.0
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Table 29 summarizes device-related adverse events (events rated as possibly, probably,
or definitely related to the test device. Among the 82 subjects treated with the
LaserComb, 9 (11.0%) had 11 device-related adverse events and 3/41 (7.3%) subjects
treated with the placebo device had four device-related adverse events.
Table 29: Summary of Device-Related1 Adverse Events
Adverse Event LaserComb
(N=82)
n (%)
Placebo
(N=41)
n (%)
P-Value
Subjects with at least one related AE 9 (11.0%) 3 (7.3%) 0.75
Dry skin 1 (1.2%) 1 (2.4%) 1.0
Dryness of scalp 0 (0%) 1 (2.4%) 0.33
Dandruff 0 (0%) 1 (2.4%) 0.33
Paresthesia 4 (4.9%) 0 (0%) 0.30
Pruritis 1 (1.2%) 0 (0%) 1.0
Urticaria 3 (3.7%) 1 (2.4%) 1.0
Vasodilatation 1 (1.2%) 0 (0%) 1.0
Vasodilatation – scalp 1 (1.2%) 0 (0%) 1.0
1 Events rated as possibly, probably, or definitely related to the test device
Table 30 summarizes adverse events by severity. No subject in the LaserComb group
reported a severe adverse event, while one subject in the placebo group (02-014) reported
severe hypertonia of the neck and a severe migraine headache.
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Table 30: Summary of Adverse Event by Severity
Adverse Event LaserComb
(N=82)
Placebo
(N=41)
Mild
n (%)
Mod.
n (%)
Severe
n (%)
Mild
n (%)
Mod.
n (%)
Severe
n (%)
Asthma 0 (0%) 1 (1.2%) 0 (0%) 0 (0%) 0 (0%) 0 (0%)
Benign prostatic
hyperplasia
0 (0%) 0 (0%) 0 (0%) 0 (0%) 1 (2.4%) 0 (0%)
Bronchitis 0 (0%) 1 (1.2%) 0 (0%) 0 (0%) 0 (0%) 0 (0%)
Cold 0 (0%) 3 (3.7%) 0 (0%) 1 (2.4%) 1 (2.4%) 0 (0%)
Dental infection 1 (1.2%) 0 (0%) 0 (0%) 0 (0%) 1 (2.4%) 0 (0%)
Depression 0 (0%) 0 (0%) 0 (0%) 1 (2.4%) 0 (0%) 0 (0%)
Dizziness 0 (0%) 0 (0%) 0 (0%) 0 (0%) 1 (2.4%) 0 (0%)
Dry skin 2 (2.4%) 0 (0%) 0 (0%) 0 (0%) 1 (2.4%) 0 (0%)
Dryness of scalp 0 (0%) 0 (0%) 0 (0%) 0 (0%) 1 (2.4%) 0 (0%)
Fever 0 (0%) 0 (0%) 0 (0%) 0 (0%) 1 (2.4%) 0 (0%)
Fracture-foot 0 (0%) 1 (1.2%) 0 (0%) 0 (0%) 0 (0%) 0 (0%)
Hoarseness 0 (0%) 1 (1.2%) 0 (0%) 0 (0%) 0 (0%) 0 (0%)
Hypercholesterolemia 0 (0%) 0 (0%) 0 (0%) 0 (0%) 1 (2.4%) 0 (0%)
Hypertension 0 (0%) 0 (0%) 0 (0%) 1 (2.4%) 0 (0%) 0 (0%)
Hypertonia-neck 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 1 (2.4%)
Infection – urinary
tract
0 (0%) 0 (0%) 0 (0%) 0 (0%) 1 (2.4%) 0 (0%)
Influenza 1 (1.2%) 1 (1.2%) 0 (0%) 0 (0%) 0 (0%) 0 (0%)
Laceration 2 (2.4%) 0 (0%) 0 (0%) 1 (2.4%) 0 (0%) 0 (0%)
Migraine 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 1 (2.4%)
Nausea 0 (0%) 0 (0%) 0 (0%) 0 (0%) 1 (2.4%) 0 (0%)
Dandruff 0 (0%) 0 (0%) 0 (0%) 1 (2.4%) 0 (0%) 0 (0%)
Paresthesia 4 (4.9%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%)
Pruritis 1 (1.2%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%)
Rash 0 (0%) 1 (1.2%) 0 (0%) 0 (0%) 0 (0%) 0 (0%)
Skin disorder – scabs 0 (0%) 1 (1.2%) 0 (0%) 0 (0%) 0 (0%) 0 (0%)
Skin irritation 1 (1.2%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%)
Sleep apnea 1 (1.2%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%)
Urinary retention 0 (0%) 0 (0%) 0 (0%) 0 (0%) 1 (2.4%) 0 (0%)
Urticaria 4 (4.9%) 0 (0%) 0 (0%) 1 (2.4%) 0 (0%) 0 (0%)
Vasodilatation 1 (1.2%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%)
Vasodilatation – scalp 1 (1.2%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%)
Table 31 summarizes adverse events by action taken. Seven adverse events in six
subjects treated with LaserComb required medication to treat an adverse event. Eight
adverse events in six subjects treated with placebo required medication to treat an adverse
event. Three adverse events in two subjects treated with LaserComb required other
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therapy to treat an adverse event, while five adverse events in three subjects treated with
placebo required other therapy to treat an adverse event.
Table 31: Summary of Adverse Event by Action Taken
Adverse Event LaserComb
(N=82)
Placebo
(N=41)
None
n (%)
Med
n (%)
Other
n (%)
None
n (%)
Med
n (%)
Other
n (%)
Asthma 0 (0%) 1 (1.2%) 0 (0%) 0 (0%) 0 (0%) 0 (0%)
Benign prostatic
hyperplasia
0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 1 (2.4%)
Bronchitis 0 (0%) 1 (1.2%) 0 (0%) 0 (0%) 0 (0%) 0 (0%)
Cold 1 (1.2%) 2 (2.4%) 0 (0%) 1 (2.4%) 1 (2.4%) 0 (0%)
Dental infection 0 (0%) 0 (0%) 1 (1.2%) 0 (0%) 1 (2.4%) 0 (0%)
Depression 0 (0%) 0 (0%) 0 (0%) 0 (0%) 1 (2.4%) 0 (0%)
Dizziness 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 1 (2.4%)
Dry skin 1 (1.2%) 0 (0%) 1 (1.2%) 1 (2.4%) 0 (0%) 0 (0%)
Dryness of scalp 0 (0%) 0 (0%) 0 (0%) 1 (2.4%) 0 (0%) 0 (0%)
Fever 0 (0%) 0 (0%) 0 (0%) 0 (0%) 1 (2.4%) 0 (0%)
Fracture-foot 0 (0%) 1 (1.2%) 0 (0%) 0 (0%) 0 (0%) 0 (0%)
Hoarseness 0 (0%) 1 (1.2%) 0 (0%) 0 (0%) 0 (0%) 0 (0%)
Hypercholesterolemia 0 (0%) 0 (0%) 0 (0%) 0 (0%) 1 (2.4%) 0 (0%)
Hypertension 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 1 (2.4%)
Hypertonia-neck 0 (0%) 0 (0%) 0 (0%) 0 (0%) 1 (2.4%) 0 (0%)
Infection – urinary
tract
0 (0%) 0 (0%) 0 (0%) 0 (0%) 1 (2.4%) 0 (0%)
Influenza 1 (1.2%) 1 (1.2%) 0 (0%) 0 (0%) 0 (0%) 0 (0%)
Laceration 2 (2.4%) 0 (0%) 0 (0%) 1 (2.4%) 0 (0%) 0 (0%)
Migraine 0 (0%) 0 (0%) 0 (0%) 0 (0%) 1 (2.4%) 0 (0%)
Nausea 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 1 (2.4%)
Dandruff 0 (0%) 0 (0%) 0 (0%) 1 (2.4%) 0 (0%) 0 (0%)
Paresthesia 4 (4.9%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%)
Pruritis 0 (0%) 0 (0%) 1 (1.2%) 0 (0%) 0 (0%) 0 (0%)
Rash 1 (1.2%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%)
Skin disorder – scabs 1 (1.2%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%)
Skin irritation 1 (1.2%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%)
Sleep apnea 1 (1.2%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%)
Urinary retention 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 1 (2.4%)
Urticaria 4 (4.9%) 0 (0%) 0 (0%) 1 (2.4%) 0 (0%) 0 (0%)
Vasodilatation 1 (1.2%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%)
Vasodilatation – scalp 1 (1.2%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%)
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Baseline and change from baseline in vital signs are summarized in Table 32 by treatment
group and scheduled visit. Changes from baseline were very small in both treatment
groups and quite similar between groups.
Table 32: Mean Baseline and Change From Baseline in Vital Signs
Study
Week
LaserComb Placebo P-Value
Systolic BP (mmHg)
Baseline N 82 41
Mean (Range) 124.7(104, 156) 124.2(102, 150) 0.81
8 N 80 40
Mean (Range) -0.7 (-28, 20) 1.7 (-14, 24) 0.23
16 N 72 38
Mean (Range) 0.9 (-30, 38) 2.7 (-18, 30) 0.43
26 N 72 40
Mean (Range) -0.3 (-22, 24) 1.9 (-28, 30) 0.30
Diastolic BP (mmHg)
Baseline N 82 41
Mean (Range) 79.3 (60, 100) 79.5 (50, 108) 0.91
8 N 80 40
Mean (Range) 0.2 (-20, 18) -0.4 (-22, 16) 0.68
16 N 72 38
Mean (Range) 0.7 (-28, 18) 1.8 (-24, 18) 0.53
26 N 72 40
Mean (Range) 0.4 (-20, 24) 1.2 (-16, 12) 0.58
Pulse Rate (bpm)
Baseline N 82 41
Mean (Range) 73.8 (56, 88) 72.4 (60, 92) 0.41
8 N 80 40
Mean (Range) -2.0 (-24, 22) -3.9 (-24, 12) 0.34
16 N 72 38
Mean (Range) -1.6 (-24, 24) -0.2 (-24, 18) 0.52
26 N 72 40
Mean (Range) -1.9 (-24, 16) -1.1 (-26, 30) 0.66
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Hairs per cm sq
Figure 1: Mean Change From Baseline in Hair Density (hairs/cm sq)
Mean Difference Between LaserComb and Placebo = 29.4 hairs/cm sq
25
20
15
10
5
0
-5
-10
-15
LaserComb Placebo
Percent of Subjects
Figure 2: Subjects With Any Hair Growth
100%
90%
80%
70%
60%
50%
40%
30%
20%
10%
0%
LaserComb Placebo
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Distribution prohibited without written consent
Percent of Subjects
Figure 3: Subjects With an Increase in Hair Density > 5 hairs/sq cm
100%
90%
80%
70%
60%
50%
40%
30%
20%
10%
0%
LaserComb Placebo
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Distribution prohibited without written consent
0
0.5
1
1.5
2
2.5
Mean Response
Figure 4: Mean Response to Overall Hair Regrowth
0 5 10152025 30
Week
LaserComb
Placebo
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Mean Response
2.5
Figure 5: Mean Response to Rate of Slowing of Hair Loss
2
1.5
1
0.5
0
0 5 10 15
Week
LaserComb Placebo
20 25 30
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Mean Response
Figure 6: Mean Response to Better General Scalp Health
1.5
1
0.5
0
0 5 10152025 30
Week
LaserComb
Placebo
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Distribution prohibited without written consent
Mean Response
Figure 7: Mean Response to Hair Feeling Thicker
2.5
2
1.5
1
0.5
0
0 5 10 15
Week
LaserComb Placebo
20 25 30
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Mean Response
Figure 8: Mean Response to More Shine to Hair
1.5
1
0.5
0
0 5 10152025 30
Week
LaserComb
Placebo
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Distribution prohibited without written consent
Mean Response
Figure 9: Mean Response to Hair Growing Faster
2.5
2
1.5
1
0.5
0
0 5 101520 2530
Week
LaserComb
Placebo
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Mean Response
Figure 10: Mean Response to More Manageable Hair
2.5
2
1.5
1
0.5
0
0 5 10 15
Week
LaserComb Placebo
20 25 30
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Distribution prohibited without written consent
Mean Response
Figure 11: Mean Response to Overall Hair Improvement
1.5
1
0.5
0
0 5 10 15
Week
LaserComb Placebo
20 25 30
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Distribution prohibited without written consent
Appendix 1
Baseline, Terminal, and Change in Hair Density (hairs/cm2), and Subjects’ Overall Assessment
Baseline Terminal Change in
Treatment Hair Hair Hair Subject
Group Subject Density Density Density Assessment
LaserComb 01-002 127.3 165.5 38.2 Moderate
LaserComb 01-003 78.9 100.6 21.6 No growth
LaserComb 01-004 45.8 66.2 20.4 No growth
LaserComb 01-007 201.2 235.5 34.4 No growth
LaserComb 01-010 64.9 63.7 -1.3 No growth
LaserComb 01-013 140.1 155.3 15.3 No growth
LaserComb 01-015 136.2 188.4 52.2 Minimal
LaserComb 01-033 31.8 64.9 33.1 No growth
LaserComb 01-035 90.4 98.0 7.6 Moderate
LaserComb 01-036 99.3 121.0 21.6 Minimal
LaserComb 01-039 211.4 155.3 -56.0 No growth
LaserComb 01-041 126.1 151.5 25.5 Moderate
LaserComb 01-042 157.9 165.5 7.6 Minimal
LaserComb 01-043 99.3 127.3 28.0 Minimal
LaserComb 01-044 56.0 62.4 6.4
LaserComb 02-002 187.2 206.3 19.1 No growth
LaserComb 02-004 157.9 169.3 11.5 Dense
LaserComb 02-005 77.7 89.1 11.5 Minimal
LaserComb 02-007 94.2 98.0 3.8 Moderate
LaserComb 02-009 113.3 131.1 17.8 No growth
LaserComb 02-011 151.5 166.8 15.3 Minimal
LaserComb 02-012 39.5 44.6 5.1 Moderate
LaserComb 02-015 161.7 164.0 2.3 No growth
LaserComb 02-031 87.9 98.0 10.2 Moderate
LaserComb 03-001 187.2 234.3 47.1 Minimal
LaserComb 03-003 151.5 166.8 15.3 No growth
LaserComb 03-004 184.6 197.4 12.7 Minimal
LaserComb 03-005 137.5 154.1 16.6 Moderate
LaserComb 03-007 215.2 229.2 14.0 Minimal
LaserComb 03-010 105.7 122.2 16.6 Minimal
LaserComb 03-012 114.6 126.1 11.5 Moderate
LaserComb 03-014 131.1 152.8 21.6 Minimal
LaserComb 03-015 188.4 215.2 26.7 Moderate
LaserComb 03-017 129.9 140.1 10.2 Moderate
LaserComb 03-020 202.4 241.9 39.5 Minimal
LaserComb 03-022 61.1 96.8 35.7 Moderate
LaserComb 03-023 89.1 101.9 12.7 No growth
LaserComb 03-025 129.9 147.7 17.8 Minimal
LaserComb 04-002 187.2 198.6 11.5 Minimal
LaserComb 04-003 191.0 198.6 7.6 Minimal
LaserComb 04-004 124.8 138.8 14.0 No growth
LaserComb 04-005 122.2 149.0 26.7 Minimal
LaserComb 04-007 152.8 170.6 17.8 No growth
LaserComb 04-008 98.0 126.1 28.0 Minimal
LaserComb 04-010 185.9 206.3 20.4 No growth
LaserComb 04-012 110.8 122.2 11.5 Minimal
LaserComb 04-014 252.1 258.5 6.4 Minimal
LaserComb 04-015 136.2 160.4 24.2 Moderate
Appendix 1
Baseline, Terminal, and Change in Hair Density (hairs/cm2), and Subjects’ Overall Assessment
Baseline Terminal Change in
Treatment Hair Hair Hair Subject
Group Subject Density Density Density Assessment
LaserComb 04-017 183.3 219.0 35.7 No growth
LaserComb 04-018 133.7 154.1 20.4 Minimal
LaserComb 04-019 132.4 132.4 0.0 No growth
LaserComb 04-021 124.8 150.2 25.5 Minimal
LaserComb 04-022 96.8 113.3 16.6 No growth
LaserComb 04-023 105.7 123.5 17.8 No growth
LaserComb 04-026 141.3 170.6 29.3 Moderate
LaserComb 04-027 155.3 193.5 38.2 No growth
LaserComb 04-028 141.3 168.1 26.7 Minimal
LaserComb 04-029 133.7 154.1 20.4 No growth
LaserComb 04-031 45.8 39.5 -6.4 Minimal
LaserComb 04-033 155.3 169.3 14.0 Minimal
LaserComb 04-034 101.9 132.4 30.6 Minimal
LaserComb 04-035 81.5 85.3 3.8 Minimal
LaserComb 04-037 22.9 28.0 5.1 Minimal
LaserComb 04-038 25.5 31.8 6.4 Minimal
LaserComb 04-040 21.6 29.3 7.6 No growth
LaserComb 04-042 68.8 90.4 21.6 Moderate
LaserComb 04-044 75.1 76.4 1.3 No growth
LaserComb 04-045 178.3 198.6 20.4 No growth
LaserComb 04-047 47.1 59.8 12.7 No growth
LaserComb 04-048 201.2 208.8 7.6 No growth
LaserComb 04-049 91.7 90.4 -1.3 No growth
LaserComb 04-050 146.4 149.0 2.5 Moderate
Placebo 01-005 107.0 107.0 0.0 Minimal
Placebo 01-008 147.7 129.9 -17.8 No growth
Placebo 01-011 78.9 68.8 -10.2 No growth
Placebo 01-014 143.9 149.0 5.1 No growth
Placebo 01-032 117.1 109.5 -7.6 No growth
Placebo 01-034 67.5 64.9 -2.5 No growth
Placebo 01-038 50.9 38.2 -12.7 No growth
Placebo 01-040 39.5 34.4 -5.1
Placebo 01-045 161.7 141.3 -20.4 No growth
Placebo 02-003 25.5 29.3 3.8 No growth
Placebo 02-006 113.3 113.3 0.0 No growth
Placebo 02-008 94.2 89.1 -5.1 Minimal
Placebo 02-010 117.1 118.4 1.3 No growth
Placebo 02-014 78.9 78.9 0.0 Minimal
Placebo 02-032 132.4 128.6 -3.8 No growth
Placebo 03-002 137.5 132.4 -5.1 Minimal
Placebo 03-006 75.1 58.6 -16.6 Minimal
Placebo 03-009 110.8 105.7 -5.1 Minimal
Placebo 03-011 119.7 122.2 2.5 Moderate
Placebo 03-013 163.0 159.2 -3.8 Minimal
Placebo 03-018 141.3 149.0 7.6 No growth
Placebo 03-019 135.0 135.0 0.0 No growth
Placebo 03-024 38.2 38.2 0.0 Minimal
Placebo 03-026 145.1 137.5 -7.6 Minimal
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Appendix 1
Baseline, Terminal, and Change in Hair Density (hairs/cm2), and Subjects’ Overall Assessment
Baseline Terminal Change in
Treatment Hair Hair Hair Subject
Group Subject Density Density Density Assessment
Placebo 04-001 169.3 149.0 -20.4 No growth
Placebo 04-006 108.2 103.1 -5.1 Minimal
Placebo 04-009 225.4 207.5 -17.8 Moderate
Placebo 04-011 101.9 95.5 -6.4 No growth
Placebo 04-013 140.1 133.7 -6.4 Minimal
Placebo 04-016 184.6 155.3 -29.3 Minimal
Placebo 04-020 142.6 87.9 -54.7 No growth
Placebo 04-024 108.2 80.2 -28.0 Minimal
Placebo 04-025 160.4 154.1 -6.4 No growth
Placebo 04-030 177.0 175.7 -1.3 No growth
Placebo 04-032 201.2 175.7 -25.5 No growth
Placebo 04-036 29.3 17.8 -11.5 Minimal
Placebo 04-039 281.4 136.2 -145.1 Minimal
Placebo 04-041 105.7 96.8 -8.9 No growth
Placebo 04-043 103.1 96.8 -6.4 Minimal
Placebo 04-046 207.5 192.3 -15.3 No growth
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